Limits...
Osmotin attenuates LPS-induced neuroinflammation and memory impairments via the TLR4/NFκB signaling pathway.

Badshah H, Ali T, Kim MO - Sci Rep (2016)

Bottom Line: Osmotin improved synaptic functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95, SNAP-25, and syntaxin-1.Osmotin also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1 and caspase-3.Overall, our studies demonstrated that osmotin prevented neuroinflammation-associated memory impairment and neurodegeneration and suggest AdipoR1 as a therapeutic target for the treatment of neuroinflammation and neurological disorders, such as AD.

View Article: PubMed Central - PubMed

Affiliation: Division of Applied Life Science (BK 21), College of Natural Sciences (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.

ABSTRACT
Toll-like receptor 4 (TLR4) signaling in the brain mediates autoimmune responses and induces neuroinflammation that results in neurodegenerative diseases, such as Alzheimer's disease (AD). The plant hormone osmotin inhibited lipopolysaccharide (LPS)-induced TLR4 downstream signaling, including activation of TLR4, CD14, IKKα/β, and NFκB, and the release of inflammatory mediators, such as COX-2, TNF-α, iNOS, and IL-1β. Immunoprecipitation demonstrated colocalization of TLR4 and AdipoR1 receptors in BV2 microglial cells, which suggests that osmotin binds to AdipoR1 and inhibits downstream TLR4 signaling. Furthermore, osmotin treatment reversed LPS-induced behavioral and memory disturbances and attenuated LPS-induced increases in the expression of AD markers, such as Aβ, APP, BACE-1, and p-Tau. Osmotin improved synaptic functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95, SNAP-25, and syntaxin-1. Osmotin also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1 and caspase-3. Overall, our studies demonstrated that osmotin prevented neuroinflammation-associated memory impairment and neurodegeneration and suggest AdipoR1 as a therapeutic target for the treatment of neuroinflammation and neurological disorders, such as AD.

No MeSH data available.


Related in: MedlinePlus

Osmotin prevents LPS-induced neuroinflammatory processes via inhibition of the TLR4-NFκB pathway (A) Shown are representative Western blots probed with TLR4, CD14, p-IKKα/β, and p-NFκB antibodies from the hippocampus of adult mice. The density values are expressed in arbitrary units as the mean ± SEM of the indicated proteins (n = 5 animals per group). (B) Shown are representative photomicrographs of immunofluorescence analyses of p-NFκB-positive cells in the experimental groups. Images are representative stains obtained in sections prepared from at least 5 animals per group. All of the panels representing the CA1, CA3, and DG regions of the hippocampus show p-NFκB-stained brain tissue at a magnification of 10× objective field (scale bar = 100 μm) and magnification of 40× objective field (scale bar = 20 μm). Symbol representation for the treatment groups and level of significance are described in the data analysis section of the Materials and Methods.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4837357&req=5

f1: Osmotin prevents LPS-induced neuroinflammatory processes via inhibition of the TLR4-NFκB pathway (A) Shown are representative Western blots probed with TLR4, CD14, p-IKKα/β, and p-NFκB antibodies from the hippocampus of adult mice. The density values are expressed in arbitrary units as the mean ± SEM of the indicated proteins (n = 5 animals per group). (B) Shown are representative photomicrographs of immunofluorescence analyses of p-NFκB-positive cells in the experimental groups. Images are representative stains obtained in sections prepared from at least 5 animals per group. All of the panels representing the CA1, CA3, and DG regions of the hippocampus show p-NFκB-stained brain tissue at a magnification of 10× objective field (scale bar = 100 μm) and magnification of 40× objective field (scale bar = 20 μm). Symbol representation for the treatment groups and level of significance are described in the data analysis section of the Materials and Methods.

Mentions: The structure-activity relationship of LPS clearly elucidated the binding of LPS with TLR4 receptors, and the crystal structure of the TLR4-MD-2-LPS complex demonstrated the involvement of TLR4 receptor signaling in the progression of LPS-induced inflammatory activities23. CD14 receptors also amplify LPS responses, and TLR4/CD14 complexes serve as LPS signaling receptors24. Western blot analysis were performed to evaluate the effect of osmotin on LPS-induced activation of TLR4 and CD14 receptors. Our results demonstrated that LPS injection significantly increased TLR4 and CD14 expression compared to the control group in the hippocampus of adult mice and that osmotin treatment significantly reduced the LPS-induced elevated TLR4 and CD14 expression (Fig. 1A).


Osmotin attenuates LPS-induced neuroinflammation and memory impairments via the TLR4/NFκB signaling pathway.

Badshah H, Ali T, Kim MO - Sci Rep (2016)

Osmotin prevents LPS-induced neuroinflammatory processes via inhibition of the TLR4-NFκB pathway (A) Shown are representative Western blots probed with TLR4, CD14, p-IKKα/β, and p-NFκB antibodies from the hippocampus of adult mice. The density values are expressed in arbitrary units as the mean ± SEM of the indicated proteins (n = 5 animals per group). (B) Shown are representative photomicrographs of immunofluorescence analyses of p-NFκB-positive cells in the experimental groups. Images are representative stains obtained in sections prepared from at least 5 animals per group. All of the panels representing the CA1, CA3, and DG regions of the hippocampus show p-NFκB-stained brain tissue at a magnification of 10× objective field (scale bar = 100 μm) and magnification of 40× objective field (scale bar = 20 μm). Symbol representation for the treatment groups and level of significance are described in the data analysis section of the Materials and Methods.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837357&req=5

f1: Osmotin prevents LPS-induced neuroinflammatory processes via inhibition of the TLR4-NFκB pathway (A) Shown are representative Western blots probed with TLR4, CD14, p-IKKα/β, and p-NFκB antibodies from the hippocampus of adult mice. The density values are expressed in arbitrary units as the mean ± SEM of the indicated proteins (n = 5 animals per group). (B) Shown are representative photomicrographs of immunofluorescence analyses of p-NFκB-positive cells in the experimental groups. Images are representative stains obtained in sections prepared from at least 5 animals per group. All of the panels representing the CA1, CA3, and DG regions of the hippocampus show p-NFκB-stained brain tissue at a magnification of 10× objective field (scale bar = 100 μm) and magnification of 40× objective field (scale bar = 20 μm). Symbol representation for the treatment groups and level of significance are described in the data analysis section of the Materials and Methods.
Mentions: The structure-activity relationship of LPS clearly elucidated the binding of LPS with TLR4 receptors, and the crystal structure of the TLR4-MD-2-LPS complex demonstrated the involvement of TLR4 receptor signaling in the progression of LPS-induced inflammatory activities23. CD14 receptors also amplify LPS responses, and TLR4/CD14 complexes serve as LPS signaling receptors24. Western blot analysis were performed to evaluate the effect of osmotin on LPS-induced activation of TLR4 and CD14 receptors. Our results demonstrated that LPS injection significantly increased TLR4 and CD14 expression compared to the control group in the hippocampus of adult mice and that osmotin treatment significantly reduced the LPS-induced elevated TLR4 and CD14 expression (Fig. 1A).

Bottom Line: Osmotin improved synaptic functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95, SNAP-25, and syntaxin-1.Osmotin also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1 and caspase-3.Overall, our studies demonstrated that osmotin prevented neuroinflammation-associated memory impairment and neurodegeneration and suggest AdipoR1 as a therapeutic target for the treatment of neuroinflammation and neurological disorders, such as AD.

View Article: PubMed Central - PubMed

Affiliation: Division of Applied Life Science (BK 21), College of Natural Sciences (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.

ABSTRACT
Toll-like receptor 4 (TLR4) signaling in the brain mediates autoimmune responses and induces neuroinflammation that results in neurodegenerative diseases, such as Alzheimer's disease (AD). The plant hormone osmotin inhibited lipopolysaccharide (LPS)-induced TLR4 downstream signaling, including activation of TLR4, CD14, IKKα/β, and NFκB, and the release of inflammatory mediators, such as COX-2, TNF-α, iNOS, and IL-1β. Immunoprecipitation demonstrated colocalization of TLR4 and AdipoR1 receptors in BV2 microglial cells, which suggests that osmotin binds to AdipoR1 and inhibits downstream TLR4 signaling. Furthermore, osmotin treatment reversed LPS-induced behavioral and memory disturbances and attenuated LPS-induced increases in the expression of AD markers, such as Aβ, APP, BACE-1, and p-Tau. Osmotin improved synaptic functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95, SNAP-25, and syntaxin-1. Osmotin also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1 and caspase-3. Overall, our studies demonstrated that osmotin prevented neuroinflammation-associated memory impairment and neurodegeneration and suggest AdipoR1 as a therapeutic target for the treatment of neuroinflammation and neurological disorders, such as AD.

No MeSH data available.


Related in: MedlinePlus